{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T04:20:56Z","timestamp":1765772456886,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T00:00:00Z","timestamp":1698364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Division of Intramural Research"},{"name":"National Institute of Allergy and Infectious Diseases (NIAID)"},{"name":"NIH-NIRT-ICER"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: Multisystem inflammatory syndrome in children (MIS-C), a sequela of severe acute respiratory syndrome coronavirus-2 infection (SARS-CoV2), has been progressively reported worldwide, with cardiac involvement being a frequent presentation. Although the clinical and immunological characteristics of MIS-C with and without cardiac involvement have been described, the immunological differences between cardiac and non-cardiac MIS-C are not well understood. Methods: The levels of type 1, type 2, type 17, other proinflammatory cytokines and CC chemokines and CXC chemokines were measured using the Magpix multiplex cytokine assay system in MIS-C children with MIS-C cardiac (MIS-C (C) (n = 88)) and MIS-C non-cardiac (MIS-C (NC) (n = 64)) abnormalities. Results: MIS-C children with cardiac manifestations presented with significantly increased levels of cytokines such as IFN-\u03b3, IL-2, TNF\u03b1, IL-5, IL-1\u03b1, IL-1\u03b2, IL-6, IL-10 and IL-12p70 and chemokines such as CCL2, CCL3, CCL11 and CXCL10 in comparison to MIS-C children without cardiac manifestations. Clustering analysis revealed that cytokines and chemokines could clearly distinguish MIS-C children with and without cardiac manifestations. In addition, these responses significantly diminished and normalized 9 months after treatment. Conclusions: This is one of the first studies characterizing and differentiating systemic inflammation in MIS-C with and without cardiac involvement from a low- and middle-income country (LMIC). Our study contributes to the existing body of evidence and advances our knowledge of the immunopathogenesis of MIS-C in children.<\/jats:p>","DOI":"10.3390\/v15112162","type":"journal-article","created":{"date-parts":[[2023,10,27]],"date-time":"2023-10-27T09:42:52Z","timestamp":1698399772000},"page":"2162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Immune Profiles in Multisystem Inflammatory Syndrome in Children with Cardiovascular Abnormalities"],"prefix":"10.3390","volume":"15","author":[{"given":"Nathella Pavan","family":"Kumar","sequence":"first","affiliation":[{"name":"ICMR\u2014National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aishwarya","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"ICMR\u2014National Institute for Research in Tuberculosis, Chennai 600031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arul","family":"Nancy","sequence":"additional","affiliation":[{"name":"National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nandhini","family":"Selvaraj","sequence":"additional","affiliation":[{"name":"National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kadar","family":"Moideen","sequence":"additional","affiliation":[{"name":"National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaik Fayaz","family":"Ahamed","sequence":"additional","affiliation":[{"name":"ICMR\u2014National Institute for Research in Tuberculosis, Chennai 600031, India"},{"name":"National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel Marriam","family":"Renji","sequence":"additional","affiliation":[{"name":"National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kandasamy","family":"Sasidaran","sequence":"additional","affiliation":[{"name":"Dr. Mehta\u2019s Children\u2019s Hospital, Chennai 600031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandip","family":"Kumar","sequence":"additional","affiliation":[{"name":"Dr. Mehta\u2019s Children\u2019s Hospital, Chennai 600031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muthiah","family":"Periyakuppan","sequence":"additional","affiliation":[{"name":"Dr. Mehta\u2019s Children\u2019s Hospital, Chennai 600031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thankgavelu","family":"Sangaralingam","sequence":"additional","affiliation":[{"name":"Dr. Mehta\u2019s Children\u2019s Hospital, Chennai 600031, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Poovazhagi","family":"Varadarajan","sequence":"additional","affiliation":[{"name":"Institute of Child Health and Hospital for Children, Chennai 600008, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8931-592X","authenticated-orcid":false,"given":"Elilarasi","family":"Chelladurai","sequence":"additional","affiliation":[{"name":"Institute of Child Health and Hospital for Children, Chennai 600008, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9783-8042","authenticated-orcid":false,"given":"Subash","family":"Babu","sequence":"additional","affiliation":[{"name":"National Institutes of Health-National Institute for Research in Tuberculosis-International Center for Excellence in Research, Chennai 600031, India"},{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2020009738","DOI":"10.1542\/peds.2020-009738","article-title":"MIS-C and Cardiac Conduction Abnormalities","volume":"146","author":"Choi","year":"2020","journal-title":"Pediatrics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1161\/CIRCULATIONAHA.120.048360","article-title":"Acute Heart Failure in Multisystem Inflammatory Syndrome in Children in the Context of Global SARS-CoV-2 Pandemic","volume":"142","author":"Belhadjer","year":"2020","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"m2094","DOI":"10.1136\/bmj.m2094","article-title":"Kawasaki-like multisystem inflammatory syndrome in children during the COVID-19 pandemic in Paris, France: Prospective observational study","volume":"369","author":"Toubiana","year":"2020","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1001\/jama.2020.10369","article-title":"Clinical Characteristics of 58 Children with a Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2","volume":"324","author":"Whittaker","year":"2020","journal-title":"JAMA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1016\/j.cell.2020.09.016","article-title":"The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19","volume":"183","author":"Consiglio","year":"2020","journal-title":"Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1007\/s12519-021-00435-y","article-title":"Similarities and differences between multiple inflammatory syndrome in children associated with COVID-19 and Kawasaki disease: Clinical presentations, diagnosis, and treatment","volume":"17","author":"Zhang","year":"2021","journal-title":"World J. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E283","DOI":"10.1148\/radiol.2020202288","article-title":"Cardiac MRI in Children with Multisystem Inflammatory Syndrome Associated with COVID-19","volume":"297","author":"Blondiaux","year":"2020","journal-title":"Radiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1161\/CIRCULATIONAHA.120.050065","article-title":"Acute Cardiovascular Manifestations in 286 Children with Multisystem Inflammatory Syndrome Associated with COVID-19 Infection in Europe","volume":"143","author":"Valverde","year":"2021","journal-title":"Circulation"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Venkataraman, A., Kumar, N.P., Hanna, L.E., Putlibai, S., Karthick, M., Rajamanikam, A., Sadasivam, K., Sundaram, B., and Babu, S. (2021). Plasma biomarker profiling of PIMS-TS, COVID-19 and SARS-CoV2 seropositive children\u2014A cross-sectional observational study from southern India. EBioMedicine, 66.","DOI":"10.1016\/j.ebiom.2021.103317"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s42399-020-00650-0","article-title":"Childhood Multisystem Inflammatory Syndrome: An Emerging Disease with Prominent Cardiovascular Involvement-A Scoping Review","volume":"3","author":"Malviya","year":"2021","journal-title":"SN Compr. Clin. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1056\/NEJMoa2021680","article-title":"Multisystem Inflammatory Syndrome in U.S. Children and Adolescents","volume":"383","author":"Feldstein","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e927","DOI":"10.1161\/CIR.0000000000000484","article-title":"Diagnosis, Treatment, and Long-Term Management of Kawasaki Disease: A Scientific Statement for Health Professionals From the American Heart Association","volume":"135","author":"McCrindle","year":"2017","journal-title":"Circulation"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1007\/s13312-020-2025-1","article-title":"Epidemiological and Clinical Profile of Pediatric Inflammatory Multisystem Syndrome\u2014Temporally Associated with SARS-CoV-2 (PIMS-TS) in Indian Children","volume":"57","author":"Dhanalakshmi","year":"2020","journal-title":"Indian Pediatr."},{"key":"ref_14","first-page":"161","article-title":"Cytokines in the systemic inflammatory response syndrome: A review","volume":"2","author":"Jaffer","year":"2010","journal-title":"HSR Proc. Intensive Care Cardiovasc. Anesth."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Nakra, N.A., Blumberg, D.A., Herrera-Guerra, A., and Lakshminrusimha, S. (2020). Multi-System Inflammatory Syndrome in Children (MIS-C) Following SARS-CoV-2 Infection: Review of Clinical Presentation, Hypothetical Pathogenesis, and Proposed Management. Children, 7.","DOI":"10.3390\/children7070069"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1056\/NEJMe2023158","article-title":"Childhood Multisystem Inflammatory Syndrome\u2014A New Challenge in the Pandemic","volume":"383","author":"Levin","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1161\/CIRCULATIONAHA.120.049836","article-title":"Review of Cardiac Involvement in Multisystem Inflammatory Syndrome in Children","volume":"143","author":"Alsaied","year":"2021","journal-title":"Circulation"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"626182","DOI":"10.3389\/fped.2020.626182","article-title":"Multisystem Inflammatory Syndrome in Children (MIS-C), a Post-viral Myocarditis and Systemic Vasculitis-A Critical Review of Its Pathogenesis and Treatment","volume":"8","author":"McMurray","year":"2020","journal-title":"Front. Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s13312-023-2887-0","article-title":"Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19\u2014Single-Center Experience","volume":"60","author":"Varadarajan","year":"2023","journal-title":"Indian Pediatr."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Ludwikowska, K.M., Moksud, N., Tracewski, P., Sokolski, M., and Szenborn, L. (2023). Cardiac Involvement in Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) in Poland. Biomedicines, 11.","DOI":"10.3390\/biomedicines11051251"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1016\/S0140-6736(20)31094-1","article-title":"Hyperinflammatory shock in children during COVID-19 pandemic","volume":"395","author":"Riphagen","year":"2020","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e017224","DOI":"10.1161\/JAHA.120.017224","article-title":"Coronavirus Disease 2019 (COVID-19) Pandemic Implications in Pediatric and Adult Congenital Heart Disease","volume":"9","author":"Alsaied","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1007\/s12098-022-04328-4","article-title":"Severity and Cardiac Involvement in Multisystem Inflammatory Syndrome in Children","volume":"89","author":"Dhaliwal","year":"2022","journal-title":"Indian J. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/infdis\/jiac304","article-title":"Enhanced Severe Acute Respiratory Syndrome Coronavirus 2 Antigen-Specific Systemic Immune Responses in Multisystem Inflammatory Syndrome in Children and Reversal After Recovery","volume":"226","author":"Kumar","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1050804","DOI":"10.3389\/fmed.2022.1050804","article-title":"Role of matrix metalloproteinases in multi-system inflammatory syndrome and acute COVID-19 in children","volume":"9","author":"Venkataraman","year":"2022","journal-title":"Front. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"ofab279","DOI":"10.1093\/ofid\/ofab279","article-title":"Systemic Inflammation and Microbial Translocation Are Characteristic Features of SARS-CoV-2-Related Multisystem Inflammatory Syndrome in Children","volume":"8","author":"Kumar","year":"2021","journal-title":"Open Forum Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s00296-020-04749-4","article-title":"Severe COVID-19, multisystem inflammatory syndrome in children, and Kawasaki disease: Immunological mechanisms, clinical manifestations and management","volume":"41","author":"Kabeerdoss","year":"2021","journal-title":"Rheumatol. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/s12098-022-04184-2","article-title":"Comparison of Multisystem Inflammatory Syndrome (MIS-C) and Dengue in Hospitalized Children","volume":"90","author":"Randhawa","year":"2023","journal-title":"Indian J. Pediatr."},{"key":"ref_29","first-page":"642","article-title":"Systemic lupus erythematosus complicated with macrophage activation syndrome mimicking COVID-19 multisystemic inflammatory syndrome in children","volume":"78","author":"Tello","year":"2021","journal-title":"Bol. Med. Hosp. Infant. Mex."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S2352-4642(21)00138-3","article-title":"6-month multidisciplinary follow-up and outcomes of patients with paediatric inflammatory multisystem syndrome (PIMS-TS) at a UK tertiary paediatric hospital: A retrospective cohort study","volume":"5","author":"Penner","year":"2021","journal-title":"Lancet Child Adolesc. Health"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/11\/2162\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:13:04Z","timestamp":1760130784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/11\/2162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,27]]},"references-count":30,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["v15112162"],"URL":"https:\/\/doi.org\/10.3390\/v15112162","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2023,10,27]]}}}